Efficacy of sub-threshold focused ultrasound irradiation against pancreatic cancer xenografts evaluated using magnetic resonance imaging
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Rui Wang1,2,*, Qian Guo1,2,*, Yini Chen1,2, Yihui Gao1,2, Lei Wu1,2, Bing Hu1,2,** and Lixin Jiang1,2,**
1Department of Ultrasonography, Shanghai Jiaotong University Affiliated No. 6 Hospital, Shanghai 200233, PR China
2Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, PR China
**These authors have contributed equally to this work and should be considered co-corresponding authors
Lixin Jiang, email: [email protected]
Bing Hu, email: [email protected]
Keywords: pancreatic cancer, MRI, nude mice, focused ultrasound ablation, xenografts
Received: April 04, 2017 Accepted: June 11, 2017 Published: July 14, 2017
We investigated the efficacy and optimal period for using magnetic resonance imaging (MRI) to detect effects of sub-threshold focused ultrasound (FUS) irradiation. Nude mice bearing pancreatic cancer xenografts were subjected to MRI and pathology examnation before, and 24 h, 48 h, 2 weeks after irradiation, which were used to evaluate therapeutic effects of FUS. Tumor volumes were lower post-treatment than control group (P < 0.05). The T1WI turbo spin echo (T1WI-TSE) sequence was similar signal before and after treatment. On T1 enhanced scanning sequence (T1WI-SPIR) imaging, ablation lesions appeared as patchy areas of low signal after 24 h and 48 h. After 2 weeks, the ablation lesions contained low signal areas with clear borders. Hematoxylin and eosin (HE) staining revealed small vessels at ablation lesions with no obvious boundary between cell injury areas and normal tumor cells areas in early-stage, while revealed obvious boundaries 2 weeks post-treatment. Terminal deoxynucleotidyl transferase-modified, dUTP nick-end labeling (TUNEL) staining showed cell apoptosis in early-stage, and revealed reduced apoptotic cells and increased necrotic cell areas 2 weeks later. These findings indicate sub-threshold FUS induces pancreatic cancer cell apoptosis and inhibits tumor growth. Contrast-enhanced MRI delineated the ablation lesions better 2 weeks post-treatment than early stage.
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